Isoxazole derivatives for use as plant growth regulators

ABSTRACT

The present invention relates to thiophene, furan and pyrrole compounds of formula (I) having plant growth regulating properties, to agricultural compositions comprising them, and to the use of said compounds for regulating plant growth.

The present invention relates to thiophene, furan and pyrrole compounds having plant growth regulating properties, to agricultural compositions comprising them, and to the use of said compounds for regulating plant growth.

Plant growth regulators (PGRs) are generally any substances or mixtures of substances intended to accelerate or retard the rate of growth or maturation, or otherwise alter the development of plants or their produce. PGRs affect growth and differentiation of plants, a process which is commonly and hereinafter referred to as “plant health”. There exists a need for further substances having PGR activity.

International patent application WO2007/075487 refers to a series of thiophene, furan and pyrrole derivatives having fungicidal properties.

It has surprisingly been found that the thiophene, furan and pyrrole compounds of the present invention exhibit plant growth regulating properties and are therefore suitable for use in agriculture for the improvement and control of plant health.

Accordingly, in a first aspect, the present invention provides for the use of a compound of the formula (I)

-   -   wherein     -   X is S, O, or NR₅;     -   R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl,         especially 2-, 3- or 4-pyridyl optionally substituted (e.g. 1,         2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,         haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,         haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl         optionally substituted (e.g. 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl,         haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro;     -   R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g. 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g. 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g. 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g. 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₄ is H; acyl (e.g., acetyl, benzoyl, phenylacetyl); haloacyl;         alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or         dialkylaminocarbonyl;     -   R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl;         arylalkyl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryloxyalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   and salts thereof; as a plant growth regulator.

Plant growth regulators can, for example, reduce plant height, stimulate seed germination, induce flowering, darken leaf coloring, change the rate of plant growth and modify the timing and efficiency of fruiting. In addition, PGRs may exhibit pronounced growth-regulating properties which can result in an increase in the yield of cultivated plants or harvested crops.

PGRs may also have a growth inhibiting action which is dependent on concentration. The growth of both monocots and dicots may be inhibited. Inhibition of the vegetative growth of many cultivated plants permits more plants to be sown in a crop area, so that a higher yield may be obtained per unit of area. Inhibition of the vegetative growth of monocot plants, e.g. cultivated plants such as cereals, is sometimes desirable and advantageous. Such a growth inhibition is of economic interest.

The use of PGRs for inhibiting the growth in height of cereals is also important, as shortening the stalks diminishes or completely eliminates the danger of lodging before harvesting. Additionally, PGRs are able to bring about a strengthening of the stalks in crops of cereals and this too counteracts lodging.

Furthermore, the present invention also provides compositions comprising the thiophene, furan and pyrrole derivatives of the present invention that improve plants, a process which is commonly and hereinafter referred to as “plant health”.

For example, advantageous properties that may be mentioned are improved crop characteristics including: emergence, crop yield, protein content, increased vigour, faster/delayed maturation, increased speed of seed emergence, improved nutrient utilization efficiency, improved nitrogen utilization efficiency, improved water use efficiency, improved oil content and /or quality, improved digestibility, faster/more even ripening, improved flavor, improved starch content, more developed root system (improved root growth), improved stress tolerance (e.g. against drought, heat, salt, light, UV, water, cold), reduced ethylene (reduced production and/or inhibition of reception), tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf color, pigment content, photosynthetic activity, less input needed (such as fertilizers or water), less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, enhanced plant vigor, increased plant stand and early and better germination.

Advantageous properties obtained, especially from treated seeds, include, for example, improved germination and field establishment, better vigor and more homogeneous field establishment.

Advantageous properties obtained, especially from foliar and/or in-furrow application include, for example, improved plant growth and plant development, better growth, more tillers, greener leafes, largers leaves, more biomass, better roots, improved stress tolerance of the plants, more grain yield, more biomass harvested, improved quality of the harvest (content of fatty acids, metabolites, oil etc), more marketable products (e.g. improved size), improved process (e.g. longer shelf-life, better extraction of compounds), improved quality of seeds (for being seeded in the following seasons for seed production); or any other advantages familiar to a person skilled in the art.

It is therefore an object of the present invention to provide compositions and methods suitable for addressing the opportunities outlined above.

The present invention provides plant-protecting active ingredients that are thiophene, furan and pyrrole compounds of formula (I) according to the invention, in particular the individual thiophene, furan and pyrrole compounds described in the description as being preferred, and mixtures with increased efficacy and to a method of improving the health of plants by applying said compounds and mixtures to the plants or the locus thereof.

The action of the compounds of formula (I) is separate to any fungicidal action. The thiophene, furan and pyrrole compounds of formula (I) according to the invention, in particular the individual thiophene, furan and pyrrole compounds described in the above description as being preferred compounds exhibit plant health properties.

The present invention also concerns compositions comprising or consisting essentially of an active compound as described herein in combination with a suitable carrier (e.g., an agricultural carrier).

The foregoing and other objects and aspects of the present invention are explained in greater detail below.

“Alkyl” as used herein refers to a saturated hydrocarbon radical which may be straight-chain or branched-chain or cyclic (cycloalkyl) and contains from 1 to 24 carbon atoms. This definition applies both when the term is used alone and when it is used as part of a compound term, such as haloalkyl and similar terms. Preferred straight chain and branched alkyl groups may contain 1 to 8 carbon atoms, more preferably 1 to 4 carbons, even more preferably, 1 to 4 carbon atoms. Representative alkyl groups include, for example, methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl, t-amyl, and 2,5-dimethylhexyl. Preferred cycloalkyl groups may contain 3 to 12 carbon atoms, more preferably 4 to 10 carbons, even more preferably, 5 to 8 carbon atoms and most preferably 5 or 6 carbon atoms. Preferred cycloalkyl groups include, for example, cyclobutyl, cyclopropyl, cyclopentyl and cyclohexyl.

“Alkenyl” as used herein, refers to a straight or branched chain hydrocarbon containing from 2 to 24 carbons, more preferably 2 to 8 carbons, yet more preferably, 2 to 6 carbon atoms, even more preferably 2 to 4 carbon atoms, and containing at least one carbon-carbon double bond. Representative alkenyl groups include, for example, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, 2-methyl-1-heptenyl and 3-decenyl.

“Alkynyl” as used herein, refers to a straight or branched chain hydrocarbon group containing from 2 to 24 carbons, more preferably 2 to 8 carbons, yet more preferably, 2 to 6 carbon atoms, even more preferably 2 to 4 carbon atoms, and containing at least one carbon-carbon triple bond. Representative alkynyl groups include, for example, acetylenyl, 1-propynyl, 2-propynyl, 3-butynyl, 2-pentynyl and 1-butynyl.

Representative alkoxy groups include, for example, methoxy, ethoxy and t-butoxy.

Representative alkylthio groups include, for example, methylthio, ethylthio, t-butylthio and hexylthio.

“Aryl” refers to an aromatic substituent which may be a single ring or multiple rings which are fused together, linked covalently or linked to a common group such as an ethylene or methylene moiety. The aromatic rings may each contain heteroatoms and hence aryl encompasses heteroaryl as used herein. Aryl moieties may be optionally substituted with 1 to 4 substituents independently selected from halogen, nitro, alkylcarboxyl, alkoxy and phenoxy. Representative examples of aryl include phenyl azulenyl, indanyl, indenyl, naphthyl, tetrahydronaphthyl, biphenyl, diphenylmethyl, 2,2-diphenyl-1-ethyl, thienyl, pyridyl and quinoxalyl. Most preferably, aryl is phenyl.

“Heteroaryl” means a cyclic, aromatic hydrocarbon containing 3 to 10 ring-atoms including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Preferred heteroaryl groups are five and six membered rings and contain from one to three heteroatoms independently selected from nitrogen, oxygen and sulphur. Heteroaryl moieties may be optionally substituted with 1 to 4 substituents independently selected from halogen, nitro, alkylcarboxyl, alkoxy and phenoxy. Examples of heteroaryl groups include furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl, tetrazolyl, triazinyl.

In addition, the term heteroaryl includes fused heteroaryl groups, for example benzimidazolyl, benzoxazolyl, imidazopyridinyl, benzoxazinyl, benzothiazinyl, oxazolopyridinyl, benzofuranyl, quinolinyl, quinazolinyl, quinoxalinyl, benzothiazolyl, phthalimido, benzofuranyl, benzodiazepinyl, indolyl, isoindolyl, isobenzofuranyl, chromenyl, xanthenyl, indolizinyl, indazolyl, purinyl, quinolizinyl, isoquinolyl, phthalazinyl, naphthyridinyl and benzo[b]thienyl.

“Heterocyclyl”, as used herein refers to a saturated or partially unsaturated cyclic hydrocarbon containing from 3 to 10 ring-atoms up to 4 of which may be hetero-atoms such as nitrogen, oxygen and sulfur. Examples of heterocyclyl groups are oxiranyl, azetidinyl, tetrahydrofuranyl, thiolanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, sulfolanyl, dioxolanyl, dihydropyranyl, tetrahydropyranyl, piperidinyl, pyrazolinyl, pyrazolidinyl, dioxanyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, azepinyl, oxazepinyl, thiazepinyl, thiazolinyl and diazapanyl.

“Acyl” includes any readily hydrolysable acyl groups, and comprises, for example, C(O)R⁶, C(O)OR⁶, C(O)NHR⁶ and C(O)NR⁶R⁷, wherein R⁶ and R⁷ are each independently selected from alkyl, alkenyl, akynyl, heterocyclyl, aryl and heteroaryl. Acyl groups may be optionally substituted with one or more, for example 1, 2, 3 or 4, halo or OR⁶ groups. Preferred acyl groups are acetyl, benzoyl and phenylacetyl.

“Halo” or “halogen” means fluoro, chloro, bromo and iodo and is preferably fluoro or chloro.

“Haloalkyl” includes monohaloalkyl, polyhaloalkyl and perhaloalkyl, for example, chloromethyl, 2-bromoethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, chlorodifluoromethyl, trichloromethyl, trifluoromethyl, pentafluoroethyl and 2-chloro-3-fluoropentyl.

“Organic base” as used herein includes, for example, triethylamine, triisobutylamine, triiooctylamine, triisodecylamine, diethanolamine, triethanolamine, pyridine, morpholine, and mixtures thereof. A preferred category of organic base is organic amines.

“Inorganic base” as used herein includes, for example, sodium carbonate, sodium bicarbonate, potassium carbonate, and mixtures thereof.

“Inert solvent” as used herein includes any suitable inert solvent including, for example, tetrahydrofuran, N-methylpyrrolidone, dimethylformamide, toluene, dimethyl ether, methyl t-butyl ether and dioxane, methylene chloride, chloroform, 1,2-dichloroethane, and mixtures thereof.

“Protic solvent” as used herein may be any suitable protic solvent including, for example, methanol, ethanol, isopropanol, n-butanol, ethylene glycol, methyl Cellosolve, ethyl Cellosolve, cyclohexanol, glycerol, diethylene glycol, triethanolamine, polyethylene glycol, sec-butanol, n-propanol and tert-butanol.

“Optionally substituted” means substituted by one or more substituents, in particular, one, two, three or four substituents. In the case where groups may be selected from a number of alternative groups, the selected groups may be the same or different.

“Agriculturally acceptable salt” means a salt the cation of which is known and accepted in the art for the formation of salts for agricultural or horticultural use. Preferably the salts are water-soluble.

The compounds of formula (I) may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula (I) may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers. There may be double bonds present in the molecule, such as C═C or C═N bonds, in which case compounds of formula (I) may exist as single isomers of mixtures of isomers. Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.

Suitable salts of the compounds of formula (I), include acid addition salts such as those with an inorganic acid such as hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid such as methane, benzene or toluene sulphonic acid. Other examples of organic carboxylic acids include haloacids such as trifluoroacetic acid.

N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in “Heterocyclic N-oxides” by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Fla., 1991.

In another aspect, the present invention provides a method of regulating plant growth of crops of useful plants, which comprises applying to said plants, to one or more parts of said plants, or to the locus thereof or plant propagation material, a compound of formula (I) as defined herein.

The preferred embodiments of the invention as defined below apply equally to each aspect and preferred aspects thereof of the invention as defined herein.

In an embodiment, the present invention relates to the use of a compound of the formula (I) as defined herein wherein said compound of formula I is selected from the group consisting of compounds of formula (Ia), compounds of formula (Ib), and compounds of formula (Ic):

-   -   wherein     -   R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g., 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g., 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl,         especially 2-, 3- or 4-pyridyl optionally substituted (e.g. 1,         2, 3 or 4 times) with halogen, alkyl, alkenyl, alkynyl,         haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,         haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl         optionally substituted (e.g. 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl,         haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro;     -   R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally         substituted (e.g. 1, 2, 3 or 4 times) with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl         optionally substituted (e.g. 1, 2, 3 or 4 times) with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g. 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g. 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g. 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl;     -   R₄ is H; acyl (e.g., acetyl, benzoyl, phenylacetyl); haloacyl;         alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or         dialkylaminocarbonyl;     -   R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl;         arylalkyl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryloxyalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         arylthioalkyl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         aryl optionally substituted (e.g., 1, 2, 3 or 4 times) with         halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro;         heteroaryl optionally substituted (e.g., 1, 2, 3 or 4 times)         with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl,         alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro;         or alkylsilyl.

In a preferred embodiment, R is H or C₁-C₈-alkyl. More preferably, R is H or C₁-C₄-alkyl. Most preferably, R is H or methyl.

In a preferred embodiment, R₁ is aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro.

Preferably, R₁ is aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, haloalkoxy, phenoxy, cyano, or nitro; or heteroaryl optionally substituted with halogen.

More preferably, R₁ is phenyl optionally substituted with halogen, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkoxy, cyano, or nitro; or furanyl, thienyl, pyridyl, or benzothienyl, each optionally substituted with halogen.

Most preferably, R₁ is 2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 4-trifluoro-methylphenyl, 4-trifluoromethoxyphenyl, 2-thienyl, 3-thienyl, 5-chloro-2-thienyl or 5-chloro-2-furyl.

In another preferred embodiment R₁ is alkyl; or arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro.

Preferably, R₁ is C₁-C₆-alkyl; or arylalkyl optionally substituted with halogen or alkyl.

More preferably, R₁ is C₁-C₆-alkyl; or phenyl-C₁-C₆-alkyl optionally substituted with halogen or C₁-C₆-alkyl.

Most preferably, R₁ is n-pentyl, t-butyl, benzyl or 4-chlorobenzyl.

In a preferred embodiment, R₂ is heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano or nitro.

Preferably, R₂ is pyridyl, pyrimidinyl or isoquinolyl, each optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano or nitro.

More preferably, R₂ is pyridyl, pyrimidinyl or isoquinolyl, each optionally substituted with halogen, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, C₁-C₆-haloalkoxy, cyano, or nitro.

Yet more preferably, R₂ is 2-, 3- or 4-pyridyl or 5-pyrimidinyl, each optionally substituted with halogen, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or C₁-C₆-alkylthio.

Most preferably, R₂ is 2-pyridyl, 3-pyridyl, or 5-pyrimidinyl, each optionally substituted with methyl, chloro, fluoro, methoxy, thiomethoxy or trifluoromethyl.

In a preferred embodiment, R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen; aryloxyalkyl optionally substituted with halogen; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, haloalkoxy, alkoxyalkynyl, cyano or nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylthio, haloalkoxy, cyano, or nitro; or alkylsilyl;

Preferably, R₃ is alkyl; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; or alkylsilyl

More preferably, R₃ is C₁-C₆-alkyl; phenyl optionally substituted with halogen, C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio, cyano or nitro; furanyl, thienyl or pyridyl, each optionally substituted with halogen, C₁-C₆-alkyl or C₁-C₆-alkoxy; or C₁-C₆-alkylsilyl.

Most preferably, R₃ is phenyl, 3-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 4-methylphenyl, 2-thienyl, 5-chloro-2-thienyl, 5-methyl-2-thienyl, 3-thienyl, t-butyl or trimethylsilyl.

In a preferred embodiment, R₄ is H, acetyl, benzoyl or phenylacetyl. Most preferably, R₄ is H.

In a preferred embodiment R₅ is H, alkyl or haloalkyl. Preferably, R₅ is C₁-C₆-alkyl, or C₁-C₆-haloalkyl. Yet more preferably, R₅ is C₁-C₄-alkyl or C₁-C₄-haloalkyl. Most preferably, R₅ is methyl.

In one preferred aspect of the present invention:

-   -   R is H or alkyl;     -   R₁ is alkyl; or arylalkyl optionally substituted with halogen,         alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy,         alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl         optionally substituted with halogen, alkyl, alkenyl, alkynyl,         haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,         haloalkylthio, cyano, or nitro; or heteroaryl optionally         substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl,         haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio,         cyano, or nitro;     -   R₂ is heteroaryl optionally substituted with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano or nitro;     -   R₃ is alkyl; aryl optionally substituted with halogen, alkyl,         alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio,         haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl         optionally substituted with halogen, alkyl, alkenyl, alkynyl,         haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy,         haloalkylthio, cyano, nitro; or alkylsilyl; and     -   R₄ is H, acetyl, benzoyl or phenylacetyl; and     -   R₅ is C₁-C₆-alkyl, or C₁-C₆-haloalkyl;         or a salt thereof.

In a more preferred aspect of the present invention:

-   -   R is H or C₁-C₄-alkyl;     -   R₁ is C₁-C₆-alkyl; or phenyl-C₁-C₆-alkyl optionally substituted         with halogen or C₁-C₆-alkyl; phenyl optionally substituted with         halogen, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl,         C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio,         C₁-C₆-haloalkoxy, cyano, or nitro; or furanyl, thienyl, pyridyl,         or benzothienyl, each optionally substituted with halogen;     -   R₂ is pyridyl, pyrimidinyl or isoquinolyl, each optionally         substituted with halogen, C₁-C₆-alkyl, C₂-C₆-alkenyl,         C₂-C₆-alkynyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio,         C₁-C₆-haloalkoxy, cyano, or nitro;     -   R₃ is C₁-C₆-alkyl; phenyl optionally substituted with halogen,         C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-alkylthio,         cyano or nitro; furanyl, thienyl or pyridyl, each optionally         substituted with halogen, C₁-C₆-alkyl or C₁-C₆-alkoxy; or         C₁-C₆-alkylsilyl;     -   R₄ is H; and     -   R₅ is C₁-C₄-alkyl or C₁-C₄-haloalkyl;         or a salt thereof.

In a yet more preferred aspect of the present invention:

-   -   R is H or methyl;     -   R₁ is n-pentyl, t-butyl, benzyl or 4-chlorobenzyl;         2-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl,         2-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl,         4-trifluoro-methylphenyl, 4-trifluoromethoxyphenyl, 2-thienyl,         3-thienyl, 5-chloro-2-thienyl or 5-chloro-2-furyl;     -   R₂ is 2-, 3- or 4-pyridyl or 5-pyrimidinyl, each optionally         substituted with halogen, C₁-C₆-haloalkyl, C₁-C₆-alkoxy or         C₁-C₆-alkylthio;     -   R₃ is phenyl, 3-chlorophenyl, 4-chlorophenyl, 4-fluorophenyl,         2,4-difluorophenyl, 3,5-difluorophenyl, 4-methylphenyl,         2-thienyl, 5-chloro-2-thienyl, 5-methyl-2-thienyl, 3-thienyl,         t-butyl or trimethylsilyl;     -   R₄ is H; and     -   R₅ is methyl;         or a salt thereof.

Preferred compounds of formula (I) for use according to the methods of the present invention are selected from:

2,4-Bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (compound 1);

4-(3-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3pyridyl)hydroxymethyl]thiophene (cpd. 2);

4-(3-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 3);

4-(4-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 4);

4-(4-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 5);

2-(4-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 6);

4-(2,4-Difluorophenyl)-2-(1,1-dimethylethyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 7);

2,4-Bis-(4-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 8);

4-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(2-thienyl)thiophene (cpd. 9);

2-(4-Chlorophenyl)-4-(5-chloro-2-thienyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 10);

4-(5-Chloro-2-thienyl)-2-(2,4-difluorophenyl)--3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 11);

2-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thiophene (cpd. 12);

2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thiophene (cpd. 13);

2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(2-thienyl)thiophene (cpd. 14);

2-(4-Butylphenyl)-4-(5-methyl-2-thienyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 15);

2,4-Bis-(2,4-Difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 16);

4-(4-Chlorophenyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 17);

2,4-Bis-(2-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 18); 2,4-Bis-(3-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 19);

2,4-Bis-(4-trifluoromethylphenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 20);

4-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(3-thienyl)thiophene (cpd. 21);

2-(5-Bromo-2-thienyl)-4-(4-chlorophenyl)-3-[(3-pyridylphydroxymethyl]thiophene (cpd. 22)

4-(4-Chlorophenyl)-2-(5-methyl-2-thienyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 23);

2-(3,5-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thiophene (cpd. 24);

2-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thiophene (cpd. 25);

2-(3,5-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 26);

2-(2,4-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 27);

2-(4-Chlorophenyl)-3-[(3-pyridyphydroxymethyl]-4-(3-thienyl)thiophene (cpd. 28);

3-[(3-Pyridyl)phydroxymethyl]-2-(2-tetrahydropyranyloxymethyl)-4-(3-thienyl)thiophene (cpd. 29);

4-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(3-thienyl)thiophene (cpd. 32);

4-(2,4-Difluorophenyl)-3-[(3-pyridyphydroxymethyl]-2-(2-thienyl)thiophene (cpd. 39);

2-(2,4-Difluorophenyl)-4-(2-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 45);

2,4-Bis-(2-Chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene (cpd. 49);

2,4-Bis-(3-Chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 50);

2,4-Bis-(Phenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 51);

2,4-Bis-(2,4-Dichlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 52);

2,4-Bis-(2-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 53);

2,4-Bis-(3-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 54);

2-(3-Chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 55);

4-(5-Chloro-2-furanyl)-2-(4-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 56);

4-(5-Chloro-2-furanyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 57);

2,4-Bis-(2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 58);

2,4-Bis-(4-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 59);

2-(3-Chlorophenyl)-4-phenyl-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 60);

2,4-Bis-(3-chloro-5-trifluoromethylphenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene (cpd. 61);

2,4-Bis-(2,5-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 62);

2,4-Bis-(4-chloro-3-fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 63);

2,4-Bis-(3-Methoxyphenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene (cpd. 64);

4-(2-Fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]-2-(2-thienyl)thiophene (cpd. 65);

2,4-Bis-(2-chloro-4-trifluoromethylphenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 66);

2,4-Bis-(4-Methoxyphenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 67);

2-(3-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]-thiophene (cpd. 68);

2-(5-Bromo-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 69);

2-(5-Chloro-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 70);

5-Chloro-2-(5-chloro-2-thienyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thio (cpd. 71);

4-(4-Chlorophenyl)-2-(2-fluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (cpd. 72);

4-(4-Chlorophenyl)-2-(3-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 73);

2-(2-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 74);

4-(2,4-Difluorophenyl)-2-(2-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 75);

2-(4-Chlorophenyl)-4-(4-chloro-2-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 76);

2-(3-Chlorophenyl)-4-(4-chloro-2-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 77);

4-(2,4-Difluorophenyl)-2-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 78);

2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymethyl]-thiophene (cpd. 175);

and salts thereof.

In a further aspect, the following preferred compounds of for use according to the methods of the present invention are selected from:

4-(3-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 3);

4-(4-Chlorophenyl)-2-(3,5-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 5);

2-(4-Chlorophenyl)-4-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 6);

4-(4-Chlorophenyl)-2-(2,4-difluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 17);

2-(2,4-Difluorophenyl)-4-(4-fluorophenyl)-3-[(3-pyridyl)phydroxymethyl]thiophene (cpd. 27);

2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymethyl]-thiophene (cpd. 175);

and salts thereof.

In a further aspect, the following preferred compound of for use according to the methods of the present invention is:

2-(2,4-Difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)phydroxymethyl]-thiophene (cpd. 175);

and salts thereof.

In a further aspect, the present invention provides a method of regulating plant growth of crops of useful plants, which comprises applying to said plants, to one or more parts of said plants, or to the locus thereof or plant propagation material, a compound of formula (I) as defined herein

In an embodiment, the present invention provides a method of regulating plant growth of crops of useful plants, which comprises one or more applications of one of more compounds of formula (I) alone or in conjunction with one or more customary plant protection formulating auxiliaries.

In another embodiment, the present invention provides a method of regulating plant growth of crops of useful plants, which comprises applying to said plants, to one or more parts of said plants, or to the locus thereof or plant propagation material, a compound of formula (I) as defined herein, wherein two or more applications are carried out in sequence, and wherein the two or more applications have the same or different concentration or combinations of compounds as defined herein or both.

In a further embodiment, the present invention provides a method of regulating plant growth of crops of useful plants, wherein the crops of useful plants are selected from cereals, rice, beets, leguminous plants, oil plants, cucumber plants, fibre plants, vegetables, plantation crops, ornamentals, vines, bushberries, caneberries, cranberries, peppermint, rhubarb, spearmint, sugar cane and turf grasses.

In a preferred embodiment of the invention, the plant growth regulating effect is an inhibition or a retardation of the plant growth.

In an especially preferred embodiment, the present invention provides an agricultural composition comprising one or more compounds of formula (I) as defined herein and one or more customary plant protection auxiliaries.

In a further aspect, the present invention is directed to the (R)-enantiomers of the compounds of formula (I), designated (R)-(I), wherein X, R, R₁, R₂, R₃, R₄ and R₅ are as defined herein; and salts thereof.

Preferred compounds of formula (R)-(I) include the (R)-enantiomers of compounds 1 to 175 of Table 1 herein.

The present invention provides the compound of formula (R)-(I) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is directed to the (S)-enantiomers of the compounds of formula (I), designated (S)-(I), wherein X, R, R₁, R₂, R₃, R₄ and R₅ are as defined herein; and salts thereof.

The present invention provides the compound of formula (S)-(I) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

Preferred compounds of formula (S)-(I) include the (S)-enantiomers of compounds 1 to 175 of Table 1 herein.

In a further aspect, the present invention is is directed to the (R)-enantiomers of the compounds of formula (la), designated (R)-(Ia), wherein R, R₁, R₂, R₃ and R₄ are as defined herein; and salts thereof.

Preferred compounds of formula (R)-(Ia) include the (R)-enantiomers of compounds 1 to 82 and 175 of Table 1 herein.

The present invention provides the compound of formula (R)-(la) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is is directed to the (R)-enantiomers of the compounds of formula (Ib), designated (R)-(lb), wherein R, R₁, R₂, R₃ and R₄ are as defined herein; and salts thereof.

Preferred compounds of formula (R)-(Ib) include the (R)-enantiomers of compounds 83 to 128 of Table 1 herein.

The present invention provides the compound of formula (R)-(Ib) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is is directed to the (R)-enantiomers of the compounds of formula (lc), designated (R)-(lc), wherein R, R₁, R₂, R₃, R₄ and R₅ are as defined herein; and salts thereof.

Preferred compounds of formula (R)-(lc) include the (R)-enantiomers of compounds 129 to 174 of Table 1 herein.

The present invention provides the compound of formula (R)-(lc) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is is directed to the (S)-enantiomers of the compounds of formula (Ia), designated (S)-(Ia), wherein R, R₁, R₂, R₃ and R₄ are as defined herein; and salts thereof.

Preferred compounds of formula (S)-(Ia) include the (S)-enantiomers of compounds 1 to 82 and 175 of Table 1 herein.

The present invention provides the compound of formula (S)-(Ia) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is is directed to the (S)-enantiomers of the compounds of formula (Ib), designated (S)-(Ib), wherein R, R₁, R₂, R₃ and R₄ are as defined herein; and salts thereof.

Preferred compounds of formula (S)-(Ib) include the (S)-enantiomers of compounds 83 to 128 of Table 1 herein.

The present invention provides the compound of formula (S)-(Ib) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

In a further aspect, the present invention is is directed to the (S)-enantiomers of the compounds of formula (Ic), designated (S)-(Ic), wherein R, R₁, R₂, R₃, R₄ and R₅ are as defined herein; and salts thereof.

Preferred compounds of formula (S)-(Ic) include the (S)-enantiomers of compounds 129 to 174 of Table 1 herein.

The present invention provides the compound of formula (S)-(Ic) as a single enantiomer having an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%.

“Plant propagation material” means the generative parts of a plant including seeds of all kinds (fruit, tubers, bulbs, grains etc), roots, rhizomes, cuttings, cut shoots and the like. Plant propagation material may also include plants and young plants which are to be transplanted after germination or after emergence from the soil.

“Locus” means the fields on which the plants to be treated are growing, or where the seeds of cultivated plants are sown, or the place where the seed will be placed into the soil.

The crops of useful plants to be protected typically comprise, for example, the following species of plants: cereals (wheat, barley, rye, oats, maize (including field corn, pop corn and sweet corn), rice, sorghum and related crops); beet (sugar beet and fodder beet); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, sunflowers); cucumber plants (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); vegetables (spinach, lettuce, asparagus, cabbages, carrots, eggplants, onions, pepper, tomatoes, potatoes, paprika, okra); plantation crops (bananas, fruit trees, rubber trees, tree nurseries), ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers); as well as other plants such as vines, bushberries (such as blueberries), caneberries, cranberries, peppermint, rhubarb, spearmint, sugar cane and turf grasses including, for example, cool-season turf grasses (for example, bluegrasses (Poa L.), such as Kentucky bluegrass (Poa pratensis L.), rough bluegrass (Poa trivialis L.), Canada bluegrass (Poa compressa L.) and annual bluegrass (Poa annua L.); bentgrasses (Agrostis L.), such as creeping bentgrass (Agrostis palustris Huds.), colonial bentgrass (Agrostis tenius Sibth.), velvet bentgrass (Agrostis canina L.) and redtop (Agrostis alba L.); fescues (Festuca L.), such as tall fescue (Festuca arundinacea Schreb.), meadow fescue (Festuca elatior L.) and fine fescues such as creeping red fescue (Festuca rubra L.), chewings fescue (Festuca rubra var. commutate Gaud.), sheep fescue (Festuca ovina L.) and hard fescue (Festuca longifolia); and ryegrasses (Lolium L.), such as perennial ryegrass (Lolium perenne L.) and annual (Italian) ryegrass (Lolium multiflorum Lam.)) and warm-season turf grasses (for example, Bermudagrasses ( Cynodon L. C. Rich), including hybrid and common Bermudagrass; Zoysiagrasses (Zoysia Willd.), St. Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze); and centipedegrass (Eremochloa ophiuroides (Munro.) Hack.)).

The term “useful plants” also includes useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as HPPD inhibitors, ALS inhibitors; for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones (e.g. imazamox) by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.

The term “useful plants” also includes useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known from toxin-producing bacteria, especially those of the genus Bacillus.

The term “useful plants” also includes useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as the so-called “pathogenesis-related proteins” (PRPs, see e.g. European patent application EP 0,392,225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from European patent applications EP 0,392,225 and EP 0,353,191, and International patent application WO 95/33818. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

The agrochemical compositions of the present invention will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula (I), 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.

Suitably, the agrochemical compositions of the present invention are applied prior to disease development. Rates and frequency of use of the formulations are those conventionally used in the art and will depend on factors such as the developmental stage of the plant and on the location, timing and application method. Advantageous rates of application are normally from 5 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably from 20 g to 600 g a.i./ha. When used as seed drenching agent, convenient rates of application are from 10 mg to 1 g of active substance per kg of seeds.

In practice, as indicated above, the agrochemical compositions comprising a compound of formula (I) are applied as a formulation containing the various adjuvants and carriers known to or used in the industry. They may therefore be formulated as granules, wettable or soluble powders, emulsifiable concentrates, coatable pastes, dusts, flowables, solutions, suspensions or emulsions, or as controlled release forms such as microcapsules. These formulations are described in more detail below and may contain from 0.5% to 95% or more by weight of the active ingredient. The optimum amount will depend on formulation, application equipment and nature of the plant to be treated.

Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.

Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.

Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate.

Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in treatment is required. Typical carriers for granular formulations include sand, fuller's earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound. Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins.

Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.

Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically 1 to 50 microns in diameter. The enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound. Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores. Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.

Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurised sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.

Suitable agricultural adjuvants and carriers that are useful in formulating the compositions of the invention in the formulation types described above are well known to those skilled in the art.

Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerine and N-methyl-2-pyrrolidinone. Water is generally the carrier of choice for the dilution of concentrates.

Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller's earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin.

A broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. These agents, when used, normally comprise from 0.1% to 15% by weight of the formulation. They can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub. 18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono and dialkyl phosphate esters.

Other adjuvants commonly utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti-foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.

In addition, further, other biocidally active ingredients or compositions may be combined with the compound of formula (I) and used in the methods of the invention and applied simultaneously or sequentially with the compound of formula (I). When applied simultaneously, these further active ingredients may be formulated together with the compound of formula (I) or mixed in, for example, the spray tank. These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides and/or plant growth regulators.

Accordingly, in one aspect, the present invention provides a composition comprising a compound of formula (I), which is compound 175 of Table 1, and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

Additionally, the present invention provides for the use of a composition in the methods of the present invention, said composition comprising a compound of formula (I), which is compound 175 of Table 1, and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

In a further aspect, the present invention provides a composition comprising a compound of formula (I), which is the (R)-enantiomer of formula (R)-(I) and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

Additionally, the present invention provides for the use of a composition in the methods of the present invention, said composition comprising a compound of formula (I), which is the (R)-enantiomer of formula (R)-(I), and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

In a further aspect, the present invention provides a composition comprising a compound of formula (I), which is the (S)-enantiomer of formula (S)-(I) and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

Additionally, the present invention provides for the use of a composition in the methods of the present invention, said composition comprising a compound of formula (I), which is the (S)-enantiomer of formula (S)-(I), and (i) a fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a plant growth regulator.

In addition, the compounds of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer). SAR inducers are known and described in, for example, U.S. Pat. No. 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.

In particular, compositions encompassed by the present invention include, for example, compositions comprising a compound of formula (I) and acibenzolar (CGA245704), a compound of formula (I) and ancymidol, a compound of formula (I) and alanycarb, a compound of formula (I) and aldimorph, a compound of formula (I) and amisulbrom, a compound of formula (I) and anilazine, a compound of formula (I) and azaconazole, a compound of formula (I) and azoxystrobin, a compound of formula (I) and benalaxyl, a compound of formula (I) and benthiavalicarb, a compound of formula (I) and benomyl, a compound of formula (I) and biloxazol, a compound of formula (I) and bitertanol, a compound of formula (I) and bixafen, a compound of formula (I) and blasticidin S, a compound of formula (I) and boscalid, a compound of formula (I) and bromuconazole, a compound of formula (I) and bupirimate, a compound of formula (I) and captafol, a compound of formula (I) and captan, a compound of formula (I) and carbendazim, a compound of formula (I) and carbendazim, a compound of formula (I) and chlorhydrate, a compound of formula (I) and carboxin, a compound of formula (I) and carpropamid, a compound of formula (I) and carvone, a compound of formula (I) and CGA41396, a compound of formula (I) and CGA41397, a compound of formula (I) and chinomethionate, a compound of formula (I) and chloroneb, a compound of formula (I) and chlorothalonil, a compound of formula (I) and chlorozolinate, a compound of formula (I) and clozylacon, a compound of formula (I) and copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate and Bordeaux mixture, a compound of formula (I) and cyflufenamid, a compound of formula (I) and cymoxanil, a compound of formula (I) and cyproconazole, a compound of formula (I) and cyprodinil, a compound of formula (I) and debacarb, a compound of formula (I) and di-2-pyridyl disulphide 1,1′-dioxide, a compound of formula (I) and dichlofluanid, a compound of formula (I) and diclomezine, a compound of formula (I) and dichlozoline, a compound of formula (I) and dichlone, a compound of formula (I) and dicloran, a compound of formula (I) and diclocymet, a compound of formula (I) and diethofencarb, a compound of formula (I) and difenoconazole, a compound of formula (I) and difenzoquat, a compound of formula (I) and diflumetorim, a compound of formula (I) and O,O-di-iso-propyl-S-benzyl thiophosphate, a compound of formula (I) and dimefluazole, a compound of formula (I) and dimetconazole, a compound of formula (I) and dimethomorph, a compound of formula (I) and dimethirimol, a compound of formula (I) and dimoxystrobin, a compound of formula (I) and diniconazole, a compound of formula (I) and dinocap, a compound of formula (I) and dithianon, a compound of formula (I) and dodecyl dimethyl ammonium chloride, a compound of formula (I) and dodemorph, a compound of formula (I) and dodine, a compound of formula (I) and doguadine, a compound of formula (I) and edifenphos, a compound of formula (I) and enestrobin, a compound of formula (I) and epoxiconazole, a compound of formula (I) and ethaboxam, a compound of formula (I) and ethirimol, a compound of formula (I) and etridiazole, a compound of formula (I) and famoxadone, a compound of formula (I) and fenamidone (RPA407213), a compound of formula (I) and fenarimol, a compound of formula (I) and fenbuconazole, a compound of formula (I) and fenfuram, a compound of formula (I) and fenhexamid (KBR2738), a compound of formula (I) and fenoxanil, a compound of formula (I) and fenpiclonil, a compound of formula (I) and fenpropidin, a compound of formula (I) and fenpropimorph, a compound of formula (I) and fentin acetate, a compound of formula (I) and fentin hydroxide, a compound of formula (I) and ferbam, a compound of formula (I) and ferimzone, a compound of formula (I) and fluazinam, a compound of formula (I) and fluopicolide, a compound of formula (I) and fludioxonil, a compound of formula (I) and fluoxastrobin, a compound of formula (I) and flumetover, a compound of formula (I) and SYP-L190 (flumorph), a compound of formula (I) and fluopyram, a compound of formula (I) and fluoroimide, a compound of formula (I) and fluquinconazole, a compound of formula (I) and flusilazole, a compound of formula (I) and flusulfamide, a compound of formula (I) and flutolanil, a compound of formula (I) and flutriafol, a compound of formula (I) and folpet, a compound of formula (I) and fosetyl-aluminium, a compound of formula (I) and fuberidazole, a compound of formula (I) and furalaxyl, a compound of formula (I) and furametpyr, a compound of formula (I) and guazatine, a compound of formula (I) and hexaconazole, a compound of formula (I) and hydroxyisoxazole, a compound of formula (I) and hymexazole, a compound of formula (I) and IKF-916 (cyazofamid), a compound of formula (I) and imazalil, a compound of formula (I) and imibenconazole, a compound of formula (I) and iminoctadine, a compound of formula (I) and iminoctadine triacetate, a compound of formula (I) and ipconazole, a compound of formula (I) and iprobenfos, a compound of formula (I) and iprodione, a compound of formula (I) and iprovalicarb (SZX0722), a compound of formula (I) and isopropanyl butyl carbamate, a compound of formula (I) and isoprothiolane, a compound of formula (I) and kasugamycin, a compound of formula (I) and kresoxim-methyl, a compound of formula (I) and LY186054, a compound of formula (I) and LY211795, a compound of formula (I) and LY248908, a compound of formula (I) and maneb, a compound of formula (I) and mancopper, a compound of formula (I) and man-cozeb, a compound of formula (I) and mandipropamid, a compound of formula (I) and mefenoxam, a compound of formula (I) and mepanipyrim, a compound of formula (I) and mepronil, a compound of formula (I) and metalaxyl, a compound of formula (I) and metconazole, a compound of formula (I) and methasulfocarb, a compound of formula (I) and metiram, a compound of formula (I) and metiram-zinc, a compound of formula (I) and metominostrobin, a compound of formula (I) and metrafenone, a compound of formula (I) and myclobutanil, a compound of formula (I) and myclozoline, a compound of formula (I) and neoasozin, a compound of formula (I) and nickel dimethyldithiocarbamate, a compound of formula (I) and nitrothal-isopropyl, a compound of formula (I) and nuarimol, a compound of formula (I) and ofurace, a compound of formula (I) and organomercury compounds, a compound of formula (I) and orysastrobin, a compound of formula (I) and oxadixyl, a compound of formula (I) and oxasulfuron, a compound of formula (I) and oxine-copper, a compound of formula (I) and oxolinic acid, a compound of formula (I) and oxpoconazole, a compound of formula (I) and oxycarboxin, a compound of formula (I) and pefurazoate, a compound of formula (I) and penconazole, a compound of formula (I) and pencycuron, a compound of formula (I) and penthiopyrad, a compound of formula (I) and phenazin oxide, a compound of formula (I) and phosdiphen, a compound of formula (I) and phosphorus acids, a compound of formula (I) and phthalide, a compound of formula (I) and picoxystrobin (ZA1963), a compound of formula (I) and polyoxin D, a compound of formula (I) and polyram, a compound of formula (I) and probenazole, a compound of formula (I) and prochloraz, a compound of formula (I) and procymidone, a compound of formula (I) and propamocarb, a compound of formula (I) and propiconazole, a compound of formula (I) and propineb, a compound of formula (I) and propionic acid, a compound of formula (I) and proquinazid, a compound of formula (I) and prothioconazole, a compound of formula (I) and pyraclostrobin, a compound of formula (I) and pyrazophos, a compound of formula (I) and pyribencarb, a compound of formula (I) and pyrifenox, a compound of formula (I) and pyrimethanil, a compound of formula (I) and pyroquilon, a compound of formula (I) and pyroxyfur, a compound of formula (I) and pyrrolnitrin, a compound of formula (I) and quaternary ammonium compounds, a compound of formula (I) and quinomethionate, a compound of formula (I) and quinoxyfen, a compound of formula (I) and quintozene, a compound of formula (I) and silthiofam, a compound of formula (I) and simeconazole, a compound of formula (I) and sipconazole (F-155), a compound of formula (I) and sodium pentachlorophenate, a compound of formula (I) and spiroxamine, a compound of formula (I) and streptomycin, a compound of formula (I) and sulphur, a compound of formula (I) and tebuconazole, a compound of formula (I) and tecloftalam, a compound of formula (I) and tecnazene, a compound of formula (I) and tetraconazole, a compound of formula (I) and thiabendazole, a compound of formula (I) and thifluzamid, a compound of formula (I) and 2-(thiocyanomethylthio)benzothiazole, a compound of formula (I) and thiophanate-methyl, a compound of formula (I) and thiram, a compound of formula (I) and tiadinil, a compound of formula (I) and timibenconazole, a compound of formula (I) and tolclofos-methyl, a compound of formula (I) and tolylfluanid, a compound of formula (I) and triadimefon, a compound of formula (I) and triadimenol, a compound of formula (I) and triazbutil, a compound of formula (I) and triazoxide, a compound of formula (I) and tricyclazole, a compound of formula (I) and tridemorph, a compound of formula (I) and trifloxystrobin (CGA279202), a compound of formula (I) and triforine, a compound of formula (I) and triflumizole, a compound of formula (I) and triticonazole, a compound of formula (I) and validamycin A, a compound of formula (I) and vapam, a compound of formula (I) and valiphenal a compound of formula (I) and vinclozolin, a compound of formula (I) and zineb, a compound of formula (I) and ziram, a compound of formula (I) and zoxamide, a compound of formula (I) and 3-[5-(4-chlorophenyl)-2,3-dimethylisoxazolidin-3-yl]pyridine, a compound of formula (I) and 5-chloro-7-(4-methylpiperidine-1-yl)-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine and a compound of formula (I) and N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl-benzsulfonamide.

Compounds of formula (I) may be prepared using the methods below.

Compositions of generic structure Ia wherein R and R₄═H may be prepared by the [3+2]-cycloaddition of an acetylenethiolate anion II and an acetylenic ketone III to give thiophene ketone IV which upon reduction provides the corresponding thiophene alcohol Ia (see L. S. Rodinova, M. L. Petrov, and A. A. Petrov, Zhurnal Organicheskoi Khimii 1981, 17(10), 2071-2075 for a related thiophene synthesis):

The [3+2]-cycloaddition reaction is carried out by preforming the acetylenethiolate in an inert solvent such as THF (tetrahydrofuran) at low temperature, preferably −78 °, and then adding it to a solution of the acetylenic ketone III in an inert solvent or solvent mixture, such as THF and acetonitrile, at temperatures ranging from 0° C. to −20° C. The acetylenethiolate II is prepared from the reaction of sulfur with a lithium salt (VI) of a terminal acetylene V (H. G. Raubenheimer, G. J. Kruger, C. F. Marais, R. Otte, and J. T. Z. Hattingh, Organometallics 1988, 7, 1853-1858) :

Lithium acetylide VI is formed by the treatment of terminal acetylene V with a strong base such as n-butyllithium in an inert solvent such as THF at low temperature, preferably from −40° C. to −78° C. Addition of sulfur to acetylide VI at low temperature (−40° C. to −78° C.) and reaction for 1.5-3 hr gives the acetylenethiolate II. Reduction of thiophene ketone IV is effected with a reducing agent such as LiAlH₄ in an inert solvent such as ether or THF, or NaBH₄ in a solvent such as ethanol at temperatures in the range of 0° C. to 20° C.

Alternatively, the Heck reaction may be employed to arylate activated thiophenes that are intermediates in the synthesis of la when R₁ and R₃ are aryl (L. Lavenot, C. Gozzi, K. IIg, I Orlova, V. Penalva, and M. Lemaire, Journal of Organometallic Chem. 1998, 567, 49-55).

Thus, thiophene-3-carboxaldehyde VII may be selectively arylated with aryl iodide R₃I in the presence of a transition metal catalyst such as a palladium(II) catalyst to give a 2-arylated intermediate VIII. A second palladium-catalyzed arylation with another aryl iodode R₁I then gives the 2,4-diarylthiophen-3-carboxaldehyde IX. Treatment of IX with

an organometallic reagent R₂M produces the compositions of generic structure Ia (R and R₄═H).

The Heck reaction is typically carried out in solvents such as acetonitrile or water, or in mixtures of the two, at temperatures in the range of 20-80° C. for 4-72 hrs. The typical palladium catalysts are palladium chloride, usually used in association with lithium chloride, or palladium acetate used with tetra-n-butylammonium bromide with or without a phosphine such as triphenylphosphine. The addition of the organometallic reagent R₂M is typically conducted in an inert solvent such as ether or THF under N₂ atmosphere at 0-20° C. for 1-5 hrs. The organometallic reagent may be an organolithium reagent, or preferably an organomagnesium reagent.

Compositions of generic structure Ia wherein R₄═H may also be prepared by the Michael addition of a substituted α-mercaptoketone X (R′═H) to acetylenic ketone III to give the dihydrothienyl intermediate XI. Dehydration of XI to thiophene XII and subsequent reduction of XII provides the composition Ia (R₄═H).

The Michael addition is carried out by reaction of the α-mercaptoketone X (R′═H) and the acetylenic ketone III in the presence of a base, preferably an organic base such as morpholine, and an inert solvent such as diethoxymethane at elevated temperatures such as reflux temperature for 1-8hrs. Alternatively, α-acetylthioketone X (R′═COCH₃) may be used in the Michael addition wherein the base such as morpholine cleaves the thioester to the requisite α-mercaptoketone X (R′═H) in situ.

Intermediate XI is efficiently dehydrated by treatment with p-toluenesulfonic acid or acetic anhydride in toluene at elevated temperatures (80-100° C.) for 12-48 hrs. to produce the thienyl ketone XII, reduction of which is accomplished as above with a reducing agent such as LiAlH₄ in an inert solvent such as ether or THF, or NaBH₄ in a solvent such as ethanol at temperatures in the range of 0° C. to 20° C.

The α-acetylthioketones X (R′═COCH₃) and α-mercaptoketones X (R′═H) are readily available by treating the corresponding α-bromoketones XIII with thioacetic acid in a basic medium to give X (R′═COCH₃), which upon treatment with aqueous base (e.g., aqueous NaOH) produces X (R′═H).

The compositions lb may be prepared from XIII (R═H) or its chloro analog by reaction with the β-ketoester XIV under base catalyzed conditions to give the dihydrofuran XV (see F. Feist, Chem, Ber. 1902, 35, 1537-44), dehydration of which produces the furan XVI. This dehydration is efficiently effected by treatment of XV with p-toluenesulfonic acid or acetic anhydride in toluene at elevated temperatures (80-100° C.) for 12-48 hrs. Reduction of furyl ester XVI to furyl alcohol XVII and subsequent oxidation to furylcarboxaldehyde XVIII followed by addition of organometallic reagent R₂Li or R₂MgX′ gives compound Ib (R₄═H) The reduction of XVI to alcohol XVII is accomplished using a hydride reagent such as LiAlH₄ or diisobutylaluminum hydride (DIBAL) in an inert solvent such as ether of THF. Oxidation of XVII to aldehyde my be effected with reagents including activated MnO₂, o-iodosobenzoic acid (IBX) in DMSO, or CrO₃/pyr in inert solvents such as dichloromethane. The addition of the organometallic reagent to aldehyde XVIII is typically conducted in an inert solvent such as ether or THF under N₂ atmosphere at 0-20° C. for 1-5 hrs. The organometallic reagent may be an organolithium reagent, or preferably an organomagnesium reagent.

Alternatively, furyl ester XVI may be hydrolyzed to furoic acid XIX under aqueous basic conditions such as aqueous NaOH or LiOH. Conversion of the acid XIX to the Weinreb amide XX may be accomplished by coupling XIX and N,O-hydroxylamine hydrochloride using 1-hydroxybenzotriazole (HOBT) and diisopropylcarbodiimide (DIC) in the presence of diisopropylethylamine (DIEA) in an inert solvent such as dichloromethane (DCM). Addition of organometallic agent R₂MgX′ to XX in an inert solvent such as ether or THF under N₂ atmosphere at 0-20° C. for 1-5 hrs gives the ketone XXI, reduction of which is accomplished as above with a reducing agent such as LiAlH₄ in an inert solvent such as ether or THF, or NaBH₄ in a solvent such as ethanol at temperatures in the range of 0° C. to 20° C. to produce compound Ib (R₄═H).

The compositions Ic may be prepared using an approach similar to that employed for the thiophenes Ia, i.e., but adding α-aminoketones XXII to the alkynylketone III in the Michael addition. Dehydration of dihydropyrrole XXIII to yield pyrrolyl ketone XXIV and subsequent reduction with LiAlH₄ or NaBH₄ gives Ic (R₄═H). Reaction conditions similar to those used to prepare the aforementioned furans lb may be employed.

Alternatively, condensation of α-aminoketone XXII and β-ketoester XIV under basic conditions gives the dihydropyrrole XXV (see L. Knorr, Chem. Ber. 1884, 17, 1635; A. H. Corwin, Heterocyclic Compounds, 1950, 1, 287), dehydration of which produces the pyrrolyl ester XXVI. Alkylation of XXVI with R₅I yields the N-substituted pyrrolyl ester XXVVII. In reactions similar to those described for the furan system, ester XXVII is converted to compound Ic (R₄═H).

Ester XXVII may also be hydrolyzed to its corresponding acid XXX and converted to its Weinreb amide XXXI as above. Addition of organometallic agent R₂MgX′ gives the ketone XXXII, reduction of which produces compound Ic (R₄═H).

The invention is illustrated by the following Examples.

EXAMPLE 1 2,4-Bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxymethyll thiophene (Compound 1)

To a solution of 273 mg (2.0 mmol) of 3-chlorophenylacetylene in 4 mL of anhydrous THF under a N₂ atmosphere at −78° C. was added 1.25 mL (2.0 mmol) of a 1.6M solution of n-butyllithium in hexane. The solution was stirred for 1.5 hr, and then 64 mg (2.0 mmol) of sulfur was added. After an additional 1.5 hr at −78° C., the red solution was warmed to room temperature and added to a solution of 400 mg (1.66 mmol) of 3-(3-chlorophenyI)-1-(3-pyridyl)-2-propyn-1-one in 4 mL of THF and 1 mL of acetonitrile. The reaction solution was stirred for 2 hr at room temperature, and was then poured into water. The aqueous layer was extracted several times with ether. The combined ether extracts were washed with saturated sodium chloride and dried over magnesium sulfate. The drying agent was filtered off, and the ether was removed by rotoevaporation. The crude product was purified by flash column chromatography on silica gel to give 185 mg (0.45 mmol) of 2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)carbonyl]thiophene.

¹H NMR (CDCl₃): 7.95 (d of q, 1), 8.56 (d of d, 1), and 8.73 ppm (d, 1). MS m/z 410.0 (M+H).

To a solution of 32 mg (0.08 mmol) of 2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)carbonyl]thiophene in 2 mL of anhydrous THF was added 10 mg (0.26 mmol) of lithium aluminum hydride. The mixture was stirred at 0° C. for 0.5 hr and was then diluted with ethyl acetate. The ethyl acetate solution was washed with water and dried over magnesium sulfate. The drying agent was filtered off, and the solvent was removed by rotoevaporation. The crude product was purified by preparative thin layer chromatography (prep TLC) to give 30 mg (0.073 mmol) 2,4-bis-(3-chlorophenyl)-3-[(3-pyridyl)hydroxy-methyl]thiophene (Compound 1) in 91% yield. ¹H NMR (CDCl₃): 5.98 (br s, 1), 7.44 (br d, 1), 8.08 (br s, 1), and 8.21 ppm (br d, 1).

MS m/z 412.0 (M+H).

EXAMPLE 2 4-(4-Chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (Compound 4)

To a solution of 137 mg (1.0 mmol) of 4-chlorophenylacetylene in 2 mL of anhydrous THF under a N₂ atmosphere at −78° C. was added 0.063 mL (1.0 mmol) of a 1.6M solution of n-butyllithium in hexane. The solution was stirred for 1.5 hr, and then 32 mg (1.0 mmol) of sulfur was added. After an additional 1.5 hr at −78° C., the red solution was warmed to −10° C. One half of the solution was added to a solution of 99 mg (0.39 mmol) of 3-(5-chloro-2-thienyl)-1-(3-pyridyl)-2-propyn-1-one in 2 mL of THF and 0.5 mL of acetonitrile. After an additional 0.5 hr, the reaction was diluted with ethyl acetate. The ethyl acetate solution was washed with saturated sodium chloride and dried over magnesium sulfate. The drying agent was filtered off, and the solvent was removed by rotoevaporation. The crude product was purified by flash column chromatography on silica gel to give 70 mg (0.17 mmol) of 4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)carbonyl]-thiophene. ¹H NMR (CDCl₃): 6.76 (d, 1), 6.95 (d, 1), 7.96 (br d, 1), 8.59 (br d, 1), and 8.73ppm (br s, 1). MS m/z 415.9 (M+H).

To a solution of 70 mg (0.17 mmol) of 4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)carbonyl]thiophene in 3 mL of anhydrous THF was added 13 mg (0.34 mmol) of lithium aluminum hydride. The mixture was stirred at 0° C. for 0.5 hr and was then diluted with ethyl acetate and a minimum amount of water to decompose the LiAlH₄. The ethyl acetate solution was decanted off and evaporated to dryness. The crude product was purified by preparative thin layer chromatography (prep TLC) to give 60 mg (0.14 mmol) 4-(4-chlorophenyl)-2-(5-chloro-2-thienyl)-3-[(3-pyridyl)hydroxymethyl]thiophene (Compound 4) in 84% yield. ¹H NMR (CDCl₃): 6.08 (br s, 1), 6.81 (d, 1), 6.87 (d, 1), 7.39 (br d, 1), 8.18 (br s, 1), and 8.30 ppm (br d, 1). MS m/z 417.9 (M+H).

EXAMPLE 3 3-(3-Chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one

To a solution of 5.0 gm (36.6 mmol) of 3-chlorophenylacetylene in 30 mL of anhydrous THF under a N₂ atmosphere at −78° C. was added 23 mL (36.6 mmol) of a 1.6M solution of n-butyllithium in hexane. The solution was stirred for 2 hr, and then a solution of 3.9 gm (36.6 mmol) of pyridine-3-carboxaldehyde in 5 mL of THF was added. The reaction mixture was stirred at −78° C. for 2 hr and then was poured into ice water. The solution was extracted several times with ether. The combined ether extracts were washed twice with aqueous sodium bisulfite solution to remove any remaining aldehyde, then with water, and finally with saturated sodium chloride solution. The ether layer was dried over magnesium sulfate. The drying agent was filtered off, and the ether was removed by rotoevaporation to give 8.5 gm (34.7 mmol) of oily product, 3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-ol.

The 8.5 gm of 3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-ol in 50 mL of DMSO was added 10.7 gm (38 mmol) of o-iodosobenzoic acid (IBX) in portions. The resulting mixture was stirred for 2 hr at room temperature, and then was diluted with ethyl acetate and water. The solution was filtered and the filtrate was extracted with ethyl acetate. The combined ethyl acetate extracts were washed consecutively with water and saturated sodium chloride solution. The ethyl acetate layer was dried over magnesium sulfate, the drying agent was filtered off, and the solvent was removed by rotoevaporation to give 6.84 gm (28.3 mmol) of brown solid 3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one in an overall 77% crude yield. 1H NMR (CDCl₃): 8.40 (d of m, 1), 8.84 (d of d, 1), and 9.40 ppm (d, 1). MS m/z 242.0 (M+H).

EXAMPLE 4 2,4-Bis-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene

To a suspension of 1.54 gm (11.1 mmol) of potassium carbonate, 1.44 gm (4.46 mmol) of tetrabutylammonium bromide, and 0.05 gm (0.22 mmol) of palladium(II) diacetate in 1.1 mL of acetonitrile/H₂O (9:1) under a N₂ atmosphere was added 1.83 gm (6.69 mmol) of 2,4-difluoro-1-iodobenzene and 0.50 gm (4.46 mmol) of thiophene-3-carboxaldehyde. The mixture was heated at 80° C. for 3 days, and then diluted with ethyl acetate. The ethyl acetate solution was washed with water and dried over magnesium sulfate. The drying agent was filtered off, and the solvent was removed by rotoevaporation to give a red-brown solid which was purified by flash column chromatography on silica gel to give a mixture of 2-(2,4-difluorophenyl)thiophene-3-carboxaldehyde and 2,4-bis-(2,4-difluorophenyl)thiophene-3-carboxaldehyde which was used in the next reaction.

To a solution of 0.41 gm (2.6 mmol) of 3-bromopyridine in 1.7 mL of anhydrous THF under a N₂ atmosphere was added 1.3 mL (2.6 mmol) of 2M i-propylmagnesium chloride in THF. After 2 hr of stirring, 0.39 gm of the above mixture of aldehydes in 2 mL of THF was added. After another 2 hrs, the reaction was diluted with water, and ethyl acetate was added to extract the products. The ethyl acetate extract was washed with saturated sodium chloride and dried over magnesium sulfate. The drying agent was filtered off, and the solvent was removed by rotoevaporation to give a mixture of products that were purified by preparative HPLC. From this reaction, 167 mg of 2-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene and 96 mg of the desired 2,4-bis-(2,4-difluorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene were isolated. For the latter, ¹H NMR (CDCl₃): 7.67 (br d of t, 1), 8.55 (d of d, 1), and 8.49 ppm (br d, 1). MS m/z 416.0 (M+H).

EXAMPLE 5 2-(3-Chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dihydrothiophene

A solution of 0.20 gm (0.83 mmol) of 3-(3-chlorophenyl)-1-(3-pyridyl)-2-propyn-1-one, 0.10 gm (0.99 mmol) of 3-mercapto-2-butanone, and 0.072 mL (0.83 mmol) of morpholine in 3 mL of diethoxymethane was heated to reflux under a N₂ atmosphere for 8 hrs. The reaction mixture was diluted with ethyl acetate, and the organic solution was washed with saturated sodium chloride solution. The ethyl acetate layer was dried over magnesium sulfate, the drying agent was filtered off, and the solvent was removed by rotoevaporation. The crude product was purified by silica gel column chromatography to yield 0.18 gm (0.53 mmol) of 2-(3-chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dihydrothiophene as a mixture of two isomers. ¹H NMR (CDCl₃): 1.56 (d,3), 1.64 (s, 3), 3.80 (t, 1), 7.82 (d of m, 1), 8.45 (d of d, 1), and 8.64 ppm (d, 1). MS m/z 346.0 (M+H).

EXAMPLE 6 2-(3-Chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophene (Compound 55)

A mixture of 0.050 gm (0.14 mmol) of 2-(3-chlorophenyl)-4,5-dimethyl-4-hydroxy-3-[(3-pyridyl)carbonyl]-4,5-dihydrothiophene as a mixture of two isomers and 0.024 mL of acetic anhydride in 1.0 mL of toluene was placed in a sealed vial and heated to 100° C. in a sand bath for 48 hrs. The crude reaction product was purified by preparative thin layer chromatography (prep TLC) to give 0.037 gm (0.11 mmol) of 2-(3-chlorophenyl)-4,5-dimethyl-3-[3-pyridylcarbonyl]thiophene. ¹H NMR (CDCl₃): 2.09 (s, 3), 2.43 (s, 3), 8.00 (d of m, 1), 8.58 (d of d, 1), and 8.78 ppm (d, 1). MS m/z 328.0 (M+H).

To a solution of 0.037 gm (0.11 mmol) of the preceding ketone, 2-(3-chlorophenyI)-4,5-dimethyl-3-[3-pyridylcarbonyl]thiophene, in 3 mL of diethyl ether was added 0.020 gm (0.45 mmol) of lithium aluminum hydride. The mixture was stirred at 0° C. for 0.5 hr and was then diluted with ethyl acetate and a minimum amount of water to decompose the LiAlH₄. The ethyl acetate solution was decanted off and evaporated to dryness. The crude product was purified by preparative thin layer chromatography (prep TLC) to give 0.032 gm (0.10 mmol) of 2-(3-chlorophenyl)-4,5-dimethyl-3-[(3-pyridyl)hydroxymethyl]thiophene (Compound 55). ¹H NMR (CDCl₃): 1.82 (s, 3), 2.31 (s, 3), 7.64 (d of m, 1), 8.41 (d, of d, 1), and 8.46ppm (br s, 1). MS m/z 330.0.0 (M+H).

The compounds of formula (I) in Table 1 may be prepared by analogous methods.

TABLE 1 Compound No. Structure Chemical Name 1

2,4-Bis-(3-chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 2

4-(3-Chlorophenyl)-2-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 3

4-(3-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 4

4-(4-Chlorophenyl)-2-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 5

4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 6

2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 7

4-(2,4-Difluorophenyl)-2- (1,1-dimethylethyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 8

2,4-Bis-(4-chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 9

4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 10

2-(4-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 11

4-(5-Chloro-2-thienyl)- 2-(2,4-difluorophenyl)-- 3-[(3-pyridyl) hydroxymethyl]-thiophene 12

2-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 13

2-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 14

2-(2,4-Difluorophenyl)-4- (5-methyl-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 15

2-(4-Butylphenyl)-4-(5- methyl-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 16

2,4-Bis-(2,4-Difluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- thiophene 17

4-(4-Chlorophenyl)-2- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 18

2,4-Bis-(2-trifluoro- methylphenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 19

2,4-Bis-(3-trifluoro- methylphenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 20

2,4-Bis-(4-trifluoro- methylphenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 21

4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 22

2-(5-Bromo-2-thienyl)-4- (4-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 23

4-(4-Chlorophenyl)-2-(5- methyl-2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 24

2-(3,5-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 25

2-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 26

2-(3,5-Difluorophenyl)-4-(4- fluorophenyl)-3-[(3-pyridyl) hydroxymethyl]-thiophene 27

2-(2,4-Difluorophenyl)-4-(4- fluorophenyl)-3-[(3-pyridyl) hydroxymethyl]-thiophene 28

2-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]-4- (3-thienyl)thiophene 29

3-[(3-Pyridyl)hydroxymethyl]- 2-(2-tetrahydropyranyloxy- methyl)-4-(3-thienyl)thiophene 30

4-(5-Chloro-2-thienyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 31

4-(5-Chloro-2-thienyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 32

4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 33

2-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 34

2-(4-Chlorophenoxymethyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 35

2-(4-Chlorophenoxymethyl)- 3-[(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 36

2-(4-Chlorophenylethyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)thiophene 37

2-(4-Chlorophenylethyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(3-thienyl)thiophene 38

4-(4-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 39

4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 40

4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(trimethylsilyl)thiophene 41

4-(4-Chlorophenyl)-2-(4- chlorophenylethyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 42

2-(4-Chlorophenylethyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 43

2-(4-Chlorophenoxymethyl)- 4-(4-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 44

2-(4-Chlorophenoxymethyl)- 4-(2,4-difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 45

2-(2,4-Difluorophenyl)- 4-(2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 46

2-(4-Chlorophenyl)-4- (2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 47

2-(4-Chlorophenyl)-4- (3-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 48

4-(3-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 49

2,4-Bis-(2-Chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 50

2,4-Bis-(3-Chlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 51

2,4-Bis-(Phenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 52

2,4-Bis-(2,4-Dichlorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- thiophene 53

2,4-Bis-(2-Fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 54

2,4-Bis-(3-Fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 55

2-(3-Chlorophenyl)-4,5- dimethyl-3-[(3-pyridyl) hydroxymethyl]-thiophene 56

4-(5-Chloro-2-furanyl)-2- (4-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 57

4-(5-Chloro-2-furanyl)-2- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 58

2,4-Bis-(2-thienyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 59

2,4-Bis-(4-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 60

2-(3-Chlorophenyl)-4- phenyl-3-[(3-pyridyl) hydroxymethyl]- thiophene 61

2,4-Bis-(3-chloro-5- trifluoromethylphenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 62

2,4-Bis-(2,5-difluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- thiophene 63

2,4-Bis-(4-chloro-3- fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 64

2,4-Bis-(3-Methoxyphenyl)- 3-[(3-pyridyl)hydroxymethyl]- thiophene 65

4-(2-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(2-thienyl)thiophene 66

2,4-Bis-(2-chloro-4- trifluoromethylphenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 67

2,4-Bis-(4-Methoxyphenyl)- 3-[(3-pyridyl)hydroxymethyl]- thiophene 68

2-(3-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 69

2-(5-Bromo-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 70

2-(5-Chloro-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 71

5-Chloro-2-(5-chloro-2- thienyl)-4-(2,4- difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 72

4-(4-Chlorophenyl)-2- (2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 73

4-(4-Chlorophenyl)-2- (3-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 74

2-(2-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 75

4-(2,4-Difluorophenyl)- 2-(2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 76

2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 77

2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- thiophene 78

4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene 79

4-(2,4-Dichlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 80

4-(4-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 81

4-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 82

4-(2-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(3-thienyl)thiophene 83

4-(4-Chlorophenyl)-2-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 84

4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 85

4-(4-Chlorophenyl)-2- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 86

4-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 2-(2-thienyl)furan 87

2,4-Bis-(4-chlorophenyl)-3- [(3-pyridyl)hydroxymethyl] furan 88

4-(4-Chlorophenyl)-2-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] furan 89

2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 90

4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 91

4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)furan 92

4-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)furan 93

2-(5-Chloro-2-thienyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 94

2-(3-Chlorophenyl)-4- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 95

2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] furan 96

2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] furan 97

2-(2-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] furan 98

4-(4-Chloro-2-fluorophenyl)- 2-(4-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 99

4-(4-Chloro-2-fluorophenyl)- 2-(3-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 100

4-(4-Chloro-2-fluorophenyl)- 2-(2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 101

4-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- 2-(3-thienyl)furan 102

4-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- 2-(2-thienyl)furan 103

4-(4-Chloro-2-fluorophenyl)- 2-(5-chloro-2-thienyl)--3-[(3- pyridyl)hydroxymethyl]furan 104

2-(4-Chlorophenyl)-4- (2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 105

2-(3-Chlorophenyl)-4- (2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 106

2-(2-Chlorophenyl)-4- (2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 107

4-(2,4-Dichlorophenyl)- 2-(4-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 108

4-(2,4-Dichlorophenyl)-2- (3-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 109

2-(2,4-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 110

2-(2,4-Dichlorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 111

2-(4-Chloro-2-fluorophenyl)- 3-[(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 112

2-(4-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 113

2-(3-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 114

2-(2-Chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 115

2-(4-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 116

2-(3-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 117

2-(2-Fluorophenyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 118

2-(3,5-Difluorophenyl)-3- [(3-pyridyl)hydroxymethyl]- 4-(2-thienyl)furan 119

4-(5-Chloro-2-thienyl)-2- (2,4-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 120

4-(5-Chloro-2-thienyl)-2- (2,4-dichlorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 121

2-(4-Chloro-2-fluorophenyl)- 4-(5-chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 122

2-(4-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 123

2-(3-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 124

2-(2-Chlorophenyl)-4-(5- chloro-2-thienyl)-3-[(3- pyridyl)hydroxymethyl] furan 125

4-(5-Chloro-2-thienyl)-2- (4-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 126

4-(5-Chloro-2-thienyl)-2- (3-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 127

4-(5-Chloro-2-thienyl)-2- (2-fluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 128

4-(5-Chloro-2-thienyl)-2- (3,5-difluorophenyl)-3-[(3- pyridyl)hydroxymethyl] furan 129

4-(4-Chlorophenyl)-2-(5- chloro-2-thienyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 130

4-(4-Chlorophenyl)-2- (3,5-difluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 131

4-(4-Chlorophenyl)-2- (2,4-difluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 132

4-(4-Chlorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]-2-(2- thienyl)pyrrole 133

2,4-Bis-(4-chlorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 134

4-(4-Chlorophenyl)-2-(4- chloro-2-fluorophenyl)-3- [(3-pyridyl)hydroxymethyl] pyrrole 135

2-(4-Chlorophenyl)-4- (2,4-difluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 136

4-(2,4-Difluorophenyl)-2- (4-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 137

4-(2,4-Difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]-2-(3- thienyl)pyrrole 138

4-(2,4-Difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]-2-(2- thienyl)pyrrole 139

2-(5-Chloro-2-thienyl)- 4-(2,4-difluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl] pyrrole 140

2-(3-Chlorophenyl)-4- (2,4-difluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl] pyrrole 141

2-(4-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 142

2-(3-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 143

2-(2-Chlorophenyl)-4-(4- chloro-2-fluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 144

4-(4-Chloro-2-fluorophenyl)- 2-(4-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 145

4-(4-Chloro-2-fluorophenyl)- 2-(3-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 146

4-(4-Chloro-2-fluorophenyl)- 2-(2-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 147

4-(4-Chloro-2-fluorophenyl)- 1-(N-methyl)-3-[(3-pyridyl) hydroxymethyl]-2-(3- thienyl)pyrrole 148

4-(4-Chloro-2-fluorophenyl)- 1-(N-methyl)-3-[(3-pyridyl) hydroxymethyl]-2-(2-thienyl) pyrrole 149

4-(4-Chloro-2-fluorophenyl)- 2-(5-chloro-2-thienyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 150

2-(4-Chlorophenyl)-4- (2,4-dichlorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 151

2-(3-Chlorophenyl)-4- (2,4-dichlorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl] pyrrole 152

2-(2-Chlorophenyl)-4- (2,4-dichlorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 153

4-(2,4-Dichlorophenyl)- 2-(4-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 154

4-(2,4-Dichlorophenyl)- 2-(3-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 155

2-(2,4-Difluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 156

2-(2,4-Dichlorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 157

2-(4-Chloro-2-fluorophenyl)- 1-(N-methyl)-3-[(3-pyridyl) hydroxymethyl]-4-(2-thienyl) pyrrole 158

2-(4-Chlorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 159

2-(3-Chlorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 160

2-(2-Chlorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 161

2-(4-Fluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 162

2-(3-Fluorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 163

2-(2-Fluorophenyl)-1- (N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 164

2-(3,5-Difluorophenyl)- 1-(N-methyl)-3-[(3- pyridyl)hydroxymethyl]- 4-(2-thienyl)pyrrole 165

4-(5-Chloro-2-thienyl)- 2-(2,4-difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 166

4-(5-Chloro-2-thienyl)- 2-(2,4-dichlorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 167

2-(4-Chloro-2-fluorophenyl)- 4-(5-chloro-2-thienyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 168

2-(4-Chlorophenyl)-4- (5-chloro-2-thienyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 169

2-(3-Chlorophenyl)-4- (5-chloro-2-thienyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 170

2-(2-Chlorophenyl)-4-(5- chloro-2-thienyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 171

4-(5-Chloro-2-thienyl)- 2-(4-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 172

4-(5-Chloro-2-thienyl)- 2-(3-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 173

4-(5-Chloro-2-thienyl)- 2-(2-fluorophenyl)-1-(N- methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 174

4-(5-Chloro-2-thienyl)-2- (3,5-difluorophenyl)-1- (N-methyl)-3-[(3-pyridyl) hydroxymethyl]pyrrole 175

2-(2,4-Difluorophenyl)- 4-(2-chlorophenyl)-3-[(3- pyridyl)hydroxymethyl]- thiophene

Compounds 1 to 175 all contain one asymmetrical carbon atom which is the carbon atom linked to one single hydroxy substituent (OH).

Biological Evaluation

EXAMPLE 7 Biological Evaluation of Plant Growth Regulation Effects on Grape

5 weeks old grape seedlings cultivar (cv.) Gutedel are treated with the formulated test compound in a spray chamber. After an incubation period of 8 days at 22° C. and 80% relative humidity (r. h.) in a greenhouse, the plant growth regulating effects are assessed.

EXAMPLE 8 Biological Evaluation of Plant Growth Regulation Effects on Wheat

2 weeks old wheat plants cultivar (cv.). Riband were treated with the formulated test compound in a spray chamber. After an incubation period of 8 days at 22° C. and 80% relative humidity (r. h.) in a greenhouse, the plant growth regulating effects were assessed.

Compound 175 showed plant height decrease at 200 ppm. 

1. (canceled)
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 13. A compound having the forumula 2-(2,4-difluorophenyl)-4-(2-chlorophenyl)-3-[(3-pyridyl)hydroxymethyl]thiophene.
 14. A compound, which is the (R)-enantiomer of the compound of formula (I) and salts thereof wherein said compound has the formula

wherein X is S, O, or NR₅; R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₄ is H; acyl; haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl; R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl;
 15. A compound, which is the (S)-enantiomer of a compound of formula (I) and salts thereof wherein said compound has the formula

wherein X is S, O, or NR₅; R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₄ is H; acyl; haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl; R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl;
 16. A method of regulating plant growth of crops of useful plants, which comprises applying to said plants, to one or more parts of said plants, or to the locus thereof or plant propagation material, a compound of formula (I) having the formula

wherein X is S, O, or NR₅; R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₄ is H; acyl; haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl; R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl;
 17. A method according to claim 16, which comprises one or more applications of one of more compounds of formula (I) alone or in conjunction with one or more customary plant protection formulating auxiliaries.
 18. A method according to claim 17 wherein two or more applications are carried out in sequence, and wherein the two or more applications have the same or different concentration or combinations of compounds of formula (I) or both.
 19. A method according to claim 16 wherein the useful crop plants are selected from the group consting of cereals, rice, beets, leguminous plants, oil plants, cucumber plants, fibre plants, vegetables, plantation crops, ornamentals, vines, bushberries, caneberries, cranberries, peppermint, rhubarb, spearmint, sugar cane and turf grasses.
 20. A method according to claim 16 wherein the plant growth regulating effect is an inhibition or a retardation of the plant growth.
 21. An agricultural composition comprising one or more compounds of formula (I) and one or more customary plant protection auxiliaries wherein said compound has the formula

wherein X is S, O, or NR₅; R is H; alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₁ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₂ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; heteroaryl, optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; 5-pyrimidinyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or 2- or 5-thiazolyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, haloalkyl, haloalkenyl, haloalkoxy, haloalkylthio, cyano, or nitro; R₃ is alkyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; R₄ is H; acyl; haloacyl; alkoxycarbonyl; aryloxycarbonyl; alkylaminocarbonyl; or dialkylaminocarbonyl; R₅ is H; alkyl; alkenyl; alkynyl; alkoxyalkyl; haloalkyl; arylalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryloxyalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; arylthioalkyl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; aryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, nitro; heteroaryl optionally substituted with halogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, alkoxy, alkylthio, haloalkoxy, haloalkylthio, cyano, or nitro; or alkylsilyl; 